Eliseo Guallar
Eliseo Guallar
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Chair and Professor of the Department of Epidemiology
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Professional overview
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Dr. Guallar is an epidemiologist whose research is focused on the study of cardiovascular disease epidemiology and prevention, with an emphasis on evaluating the role of environmental and nutritional exposures in the development of cardiovascular disease. This research has made critically important and novel contributions to our understanding of risk factors for chronic disease both in the US and globally. He has published seminal articles and is a leading figure in an emerging field highlighting the risks of exposure to levels of metals previously considered safe for cardiovascular health. In addition to his work in toxic metals, Dr. Guallar has made important contributions to understanding the effects of certain micronutrients and vitamin supplements on cardiovascular disease risk and outcomes. Publications in this area were influential in changing consumer habits and attitudes towards these products. Much of this research has been funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, the American Heart Association, the CDC, and other funders.
Dr. Guallar was the founding director of the Center for Clinical Epidemiology at the Samsung Medical Center and a lead investigator of the Kangbuk Samsung Cohort Study at the Kangbuk Samsung Hospital since its inception in 2010. Dr. Guallar has published over 500 research papers in peer-reviewed journals. He is also a Deputy Editor for Methods at the Annals of Internal Medicine and a past member and Chair of the Cancer, Heart, and Sleep Study Section at the National Institutes of Health.
Prior to teaching at NYU, Dr. Guallar was a Professor of Epidemiology and Medicine at the Johns Hopkins University Bloomberg School of Public Health and a core faculty member of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins. In the Department of Epidemiology, Dr. Guallar was the Director of the Environmental and Occupational Area of Concentration and the Co-Director of the PhD Program. Dr. Guallar was also an adjunct Professor at the Department of Clinical Research Design and Evaluation of the Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, in Seoul, Korea.
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Education
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Diploma of English, Spanish Official School of Languages at Zaragoza (Escuela Oficial de Idiomas de Zaragoza), Zaragoza, SpainMD, University of Zaragoza, Zaragoza, SpainMPH, University of Minnesota, Minneapolis, MNDrPH, Harvard University, Boston, MA
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Honors and awards
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Six Honor Calls in the MD Program, University of Zaragoza School of Medicine (1981)Fellow of Spain’s Program of Training of Graduate Research of the Ministry of Education and Science, University of Zaragoza (1988)Fulbright Scholar, sponsored by Spain’s Ministry of Health and Consumer Affairs (1989)Faculty Innovation Award, Johns Hopkins University Bloomberg School of Public Health (2001)Scientist Development Award, American Heart Association (2002)Fellow of the American Heart Association, Council on Epidemiology and Prevention (2013)Advising, Mentoring, and Teaching Recognition Award 2014 – 2015, Johns Hopkins University Bloomberg School of Public Health (2015)High Impact Research Icon, University of Malaya (2015)
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Publications
Publications
Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
AbstractHong, Y. S., Pasca, S., Shi, W., Puiu, D., Lake, N. J., Lek, M., Ru, M., Grove, M. L., Prizment, A., Joshu, C. E., Platz, E. A., Guallar, E., Arking, D. E., & Gondek, L. P. (n.d.).Publication year
2024Journal title
Nature communicationsVolume
15Issue
1AbstractClonal hematopoiesis of indeterminate potential is the primary pathogenic risk factor for myeloid neoplasms, while heteroplasmy (mutations in a subset of cellular mitochondrial DNA) is another marker of clonal expansion associated with hematological malignancies. We explore how these two markers relate and influence myeloid neoplasms incidence, and their role in risk stratification. We find that heteroplasmy is more common in individuals with clonal hematopoiesis of indeterminate potential, particularly those with higher variant allele fractions, multiple mutations, or spliceosome machinery mutations. Individuals with both markers have a higher risk of myeloid neoplasms than those with either alone. Furthermore, heteroplasmic variants with higher predicted deleteriousness increase the risk of myeloid neoplasms. Incorporating heteroplasmy in an existing risk score model for individuals with clonal hematopoiesis of indeterminate potential significantly improves sensitivity and better identifies high-risk groups. This suggests heteroplasmy as a clonal expansion marker and potentially as a biomarker for myeloid neoplasms development.Obstructive Sleep Apnea and Its Influence on Intracranial Aneurysm
AbstractJung, T. Y., Lee, E., Park, M., Lee, J. Y., Hong, Y. S., Cho, J., Guallar, E., Hong, S. D., Jung, Y. G., Gu, S., Ryoo, J. W., Joo, E. Y., Yeon, J. Y., Ryu, G., & Kim, H. Y. (n.d.).Publication year
2024Journal title
Journal of Clinical MedicineVolume
13Issue
1AbstractObstructive sleep apnea syndrome (OSAS) is associated with cerebrovascular disease, which can lead to life-threatening outcomes. The purpose of the study was to investigate the relationship between OSAS and comorbid intracranial aneurysms. We retrospectively reviewed 564 patients who underwent a polysomnography and brain magnetic resonance angiography as part of their health checkup. We calculated the prevalence of an intracranial aneurysm and OSAS in patients and measured the size of the intracranial aneurysm if present. The mean patient age was 55.6 ± 8.5 years, and 82.3% of them were men. The prevalence of an intracranial aneurysm in patients with OSAS was 12.1%, which is significantly higher than patients with non-OSAS (5.9%, p = 0.031). Patients with OSAS had a much higher prevalence of intracranial aneurysms, after adjusting all possible confounding factors such as age, sex, smoking status, alcohol drinking, and body mass index (odds ratio: 2.32; 95% confidence interval: 1.07–5.04). Additionally, the OSAS group had noticeably larger aneurysms compared with those of the non-OSAS group (3.2 ± 2.0 mm vs. 2.0 ± 0.4 mm, p = 0.013). We found a significant association between OSAS and intracranial aneurysms. OSAS could be another risk factor for the development of intracranial aneurysms.Optimal Antithrombotic Therapy Beyond 1-Year After Coronary Revascularization in Patients With Atrial Fibrillation
AbstractKim, J., Kang, D., Kim, H., Park, H., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).Publication year
2024Journal title
Journal of Korean Medical ScienceVolume
39Issue
24AbstractBackground: Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data. Methods: Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. Results: Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88–1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62–0.97; P = 0.024). Conclusion: As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.Overactive bladder and cognitive impairment in middle-aged women : A cross-sectional study
AbstractPark, J., Chang, Y., Choi, H. R., Kim, J. H., Seo, S. W., Ryu, H. J., Cho, Y., Kim, C., Kwon, R., Lim, G. Y., Ahn, J., Kim, K. H., Kim, H., Hong, Y. S., Zhao, D., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).Publication year
2024Journal title
MaturitasVolume
187AbstractBackground: Overactive bladder (OAB) is a common condition in middle-aged and older women. It has been reported to be potentially linked to cognitive decline, particularly in older adults. This study investigated the association between OAB symptoms and cognitive impairment in middle-aged women. Materials and methods: This cross-sectional study had a sample of 1652 women (mean age 49.3 ± 2.8 years) who were not taking medication for either urinary tract infection or OAB. OAB symptoms and cognitive function were evaluated by self-administered questionnaires: the Overactive Bladder Symptom Score and the Alzheimer's disease 8. Logistic regression models estimated prevalence ratios (PRs) with 95 % confidence intervals (CI) for cognitive impairment according to the presence/absence of OAB. Mediation analyses assessed the impact of poor sleep quality on this association. Results: Cognitive impairment was more prevalent in women with OAB than in those without OAB (multivariable-adjusted PR: 1.88 [95 % CI: 1.52–2.24]). Women experiencing nocturia (≥twice a night), urinary urgency at least once a week, and urgency urinary incontinence at least once a week had multivariable-adjusted PRs (95 % CI) for cognitive impairment of 2.08 (1.50–2.65), 2.12 (1.66–2.58), and 1.75 (1.17–2.34), respectively. Poor sleep quality mediated 10.81 % [95 % CI: 4.55–19.44 %] of the relationship between OAB and cognitive impairment. Conclusions: Among middle-aged women not taking OAB medications, OAB symptoms were associated with cognitive impairment, partly because of poor sleep quality. Further research is needed to determine whether early screening of patients with OAB can help identify those susceptible to cognitive impairment associated with OAB medication and if preventive measures should be targeted at this group.Scalp Cooling in Preventing Persistent Chemotherapy-Induced Alopecia : A Randomized Controlled Trial
AbstractKang, D., Cho, J., Zhao, D., Kim, J., Kim, N., Kim, H., Kim, S., Kim, J. Y., Park, Y. H., Im, Y. H., Guallar, E., & Ahn, J. S. (n.d.).Publication year
2024Journal title
Journal of Clinical OncologyVolume
42Issue
26Page(s)
3115-3122AbstractPURPOSE Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 mm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was –3.3 hairs/cm2. At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was –3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.Smoking habit change after cancer diagnosis : effect on cardiovascular risk
AbstractLee, H. H., Lee, H., Bhatt, D. L., Lee, G. B., Han, J., Shin, D. W., Kang, D., Youn, J. C., Guallar, E., Cho, J., & Kim, H. C. (n.d.).Publication year
2024Journal title
European Heart JournalVolume
45Issue
2Page(s)
132-135Abstract~The association of blood eosinophil counts and FEV1 decline : a cohort study
AbstractHong, Y. S., Park, H. Y., Ryu, S., Shin, S. H., Zhao, D., Singh, D., Guallar, E., Cho, J., Chang, Y., & Lim, S. Y. (n.d.).Publication year
2024Journal title
European Respiratory JournalVolume
63Issue
5AbstractBackground Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. Methods This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. Results During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil countsUtility of multimodal longitudinal imaging data for dynamic prediction of cardiovascular and renal disease : the CARDIA study
AbstractNguyen, H., Vasconcellos, H. D., Keck, K., Carr, J., Launer, L. J., Guallar, E., Lima, J. A., & Ambale-Venkatesh, B. (n.d.).Publication year
2024Journal title
Frontiers in RadiologyVolume
4AbstractBackground: Medical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD). Methods: In a multi-centered cohort of 5,114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy x-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985–2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors. Results: Longitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors; best model's C-index = 0.80–0.83 up to 20 years from baseline) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10–15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction. Conclusions: Longitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.Vessel Wall Imaging Features of Spontaneous Intracranial Carotid Artery Dissection
AbstractWasserman, B. A., Qiao, Y., Yang, W., Guallar, E., Romero, M. E., Virmani, R., & Zeiler, S. R. (n.d.).Publication year
2024Journal title
NeurologyVolume
102Issue
12AbstractBackground and ObjectivesIntracranial dissection is an important cause of stroke often with nonspecific angiographic features. Vessel wall imaging (VWI) can detect dissections, but intracranial applications remain unvalidated by pathologic specimens. We sought to determine the ability of VWI to identify the rarely reported spontaneous intracranial carotid dissection (sICD) guided by postmortem validation.MethodsVWI features of sICD, validated by postmortem specimen analysis in 1 patient, included luminal enhancement within a hypoenhancing outer wall, narrowing the mid to distal ophthalmic (C6) segment, relatively sparing the communicating (C7) segment. VWI examinations were reviewed to identify patients (1) with matching imaging features, (2) no evidence of other vasculopathies (i.e., inflammatory, intracranial atherosclerotic disease [ICAD]), and (3) adequate image quality. These sICD VWI features were compared with those in patients with known ICAD causing similar narrowing of C6 and relative sparing of C7 by a Fisher exact test accounting for multiple samples.ResultsAmong 407 VWI examinations, 8 patients were identified with 14 sICDs, all women aged 30-56 years, 6 (75%) bilateral. All patients with sICD had risk factors of dissection (e.g., recently postpartum, fibromuscular dysplasia, and hypertension) and 3 (37.5%) had intracranial dissections elsewhere. Seven (87.5%) were diagnosed as moyamoya syndrome on initial angiography. Enhancing lesions varied from thin flap-like defects (n = 6) to thick tissue along the superolateral wall of the internal carotid artery, within the hypoenhancing outer wall. Compared with 10 intracranial carotid plaques in 8 patients with ICAD, sICD demonstrated stronger (84.6% vs 20.0%, p = 0.003-0.025) and more homogeneous (61.5% vs 0.0%, p = 0.005-0.069) enhancement and less positive remodeling (0.0% vs 60.0%, p = 0.004-0.09). T1 hyperintensity was identified in 5 sICDs in 3 patients but not identified in ICAD. Three patients with serial imaging (8- to 39.8-month maximum intervals) revealed little to no changes in stenosis, wall thickening, or enhancement.DiscussionsICD is distinguishable on VWI from ICAD by enhancement characteristics, less positive remodeling, and clinical parameters. These VWI features should raise suspicion especially in young women with risk factors of dissection. Temporal stability and a lack of T1 hyperintensity should not discourage diagnosing sICD.Air pollution and mortality in patients with chronic obstructive pulmonary disease : a cohort study in South Korea
AbstractKang, S., Hong, Y. S., Park, J., Kang, D., Kim, H., Lee, J., Kim, W., Kang, S. W., Guallar, E., Cho, J., & Park, H. Y. (n.d.).Publication year
2023Journal title
Therapeutic Advances in Chronic DiseaseVolume
14AbstractBackground: Evidence on whether long-term exposure to air pollution increases the mortality risk in patients with chronic obstructive pulmonary disease (COPD) is limited. Objectives: We aimed to investigate the associations of long-term exposure to particulate matter with diameterAssociation of Eating and Sleeping Intervals With Weight Change Over Time : The Daily24 Cohort
AbstractZhao, D., Guallar, E., Woolf, T. B., Martin, L., Lehmann, H., Coughlin, J., Holzhauer, K., Goheer, A. A., McTigue, K. M., Lent, M. R., Hawkins, M., Clark, J. M., & Bennett, W. L. (n.d.).Publication year
2023Journal title
Journal of the American Heart AssociationVolume
12Issue
3AbstractBACKGROUND: We aim to evaluate the association between meal intervals and weight trajectory among adults from a clinical cohort. METHODS AND RESULTS: This is a multisite prospective cohort study of adults recruited from 3 health systems. Over the 6-month study period, 547 participants downloaded and used a mobile application to record the timing of meals and sleep for at least 1 day. We obtained information on weight and comorbidities at each outpatient visit from electronic health records for up to 10 years before until 10 months after baseline. We used mixed linear regression to model weight trajectories. Mean age was 51.1 (SD 15.0) years, and body mass index was 30.8 (SD 7.8) kg/m2; 77.9% were women, and 77.5% reported White race. Mean interval from first to last meal was 11.5 (2.3) hours and was not associated with weight change. The number of meals per day was positively associated with weight change. The average difference in annual weight change (95% CI) associated with an increase of 1 daily meal was 0.28 kg (0.02–0.53). CONCLUSIONS: Number of daily meals was positively associated with weight change over 6 years. Our findings did not support the use of time-restricted eating as a strategy for long-term weight loss in a general medical population.Association of single and joint metals with albuminuria and estimated glomerular filtration longitudinal change in middle-aged adults from Spain : The Aragon workers health study
AbstractGrau-Perez, M., Domingo-Relloso, A., Garcia-Barrera, T., Gomez-Ariza, J. L., Leon-Latre, M., Casasnovas, J. A., Moreno-Franco, B., Laclaustra, M., Guallar, E., Navas-Acien, A., Pastor-Barriuso, R., Redon, J., & Tellez-Plaza, M. (n.d.).Publication year
2023Journal title
Environmental PollutionVolume
318AbstractThe nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 μg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu–Zn–As–Ba–Ti–U–V–W and Co–Cd–Cr–Sb–V–W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population.Associations of urinary isoprostanes with measures of subclinical atherosclerosis : The Multi-Ethnic Study of Atherosclerosis (MESA)
AbstractWallace, R. L., Ogunmoroti, O., Zhao, D., Vaidya, D., Heravi, A., Guallar, E., Ndumele, C. E., Lima, J. A., Ouyang, P., Budoff, M. J., Allison, M., Thomas, I., Fashanu, O. E., Hoogeveen, R., Post, W. S., & Michos, E. D. (n.d.).Publication year
2023Journal title
Atherosclerosis PlusVolume
51Page(s)
13-21AbstractBackground: Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. Methods: Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. Results: In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. Conclusions: Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.Comparison Between Fimasartan Versus Other Angiotensin Receptor Blockers in Patients With Heart Failure After Acute Myocardial Infarction
AbstractKim, J., Kang, D., Kim, S. E., Park, H., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).Publication year
2023Journal title
Journal of Korean Medical ScienceVolume
38Issue
25AbstractBackgrounds: Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. Methods: Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. Results: Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0–3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46–1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30–1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49–3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27–1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18–1.96). Conclusion: In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.Corrigendum to Association Between Retinopathy of Prematurity in Very-Low-Birth-Weight Infants and Neurodevelopmental Impairment. Am J Ophthalmol 2022;244;205–215 (American Journal of Ophthalmology (2022) 244 (205–215), (S0002939422003129), (10.1016/j.ajo.2022.08.010))
AbstractHan, G., Lim, D. H., Kang, D., Cho, J., Guallar, E., Chang, Y. S., Chung, T. Y., Kim, S. J., & Park, W. S. (n.d.).Publication year
2023Journal title
American Journal of OphthalmologyVolume
248Page(s)
179AbstractThe authors regret that in the December 2022 issue, the Funding/Support section of the article above should have included the following funding information: This research was supported by a fund (2022-ER0603-00#) by Research of the Korea National Institute of Health.Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality
AbstractHong, Y. S., Battle, S. L., Shi, W., Puiu, D., Pillalamarri, V., Xie, J., Pankratz, N., Lake, N. J., Lek, M., Rotter, J. I., Rich, S. S., Kooperberg, C., Reiner, A. P., Auer, P. L., Heard-Costa, N., Liu, C., Lai, M., Murabito, J. M., Levy, D., … Arking, D. E. (n.d.).Publication year
2023Journal title
Nature communicationsVolume
14Issue
1AbstractMitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.Effect of Anemia on Physical Function and Physical Activity in CKD : The National Health and Nutrition Examination Survey, 1999-2016
AbstractFarag, Y. M., Blasco-Colmenares, E., Zhao, D., Sanon, M., Guallar, E., & Finkelstein, F. O. (n.d.).Publication year
2023Journal title
Kidney360Volume
4Issue
9Page(s)
E1212-E1222AbstractKey PointsIn a large sample representative of the US adult noninstitutionalized population, among participants with CKD stages 3-5, anemia was associated with a significantly lower level of physical activity.The presence of CKD and anemia showed a positive interaction on physical functioning outcomes. Among participants with CKD, physical functioning was worse in patients with anemia compared with those without anemia.BackgroundCKD is a major public health problem worldwide. Anemia, a frequent and treatable complication of CKD, is associated with decreased physical functioning and physical activity. The objective of this study was to evaluate the joint association of CKD and anemia with physical functioning and physical activity in a representative sample of the US population.MethodsCross-sectional study using the National Health and Nutrition Examination Survey (NHANES) 1999-2016 for physical functioning outcomes (N=33,300) and NHANES 2007-2016 for physical activity (N=22,933). The NHANES physical functioning questionnaire included 19 items. The NHANES physical activity questionnaire captured work-related, leisure-time, and sedentary activities. Higher physical functioning scores represent worse function. CKD was classified using Kidney Disease Outcomes Quality Initiative 2002 criteria, and anemia was defined using the World Health Organization criteria.ResultsThe adjusted mean differences (95% confidence interval) in overall physical functioning score comparing participants with anemia with those without anemia among participants with no CKD, CKD stages 1-2, and stages 3-5 were 0.5 (-0.1 to 1.0), 1.5 (0.2 to 2.8), and 3.6 (2.0 to 5.2). Anemia and CKD showed a supra-additive interaction for all physical functioning outcomes among participants in CKD stages 3-5. The prevalence of high physical activity was also lower in participants with anemia compared with those without anemia among participants in CKD stages 3-5 (adjusted prevalence ratio, 0.74; 95% confidence interval, 0.54 to 1.01).ConclusionsCKD and anemia were associated with impairments in physical functioning and reduced physical activity. For physical functioning outcomes, the combined presence of CKD and of anemia showed a stronger effect than what was expected from their independent effects.Long-Term Air Pollution Exposure and Mitochondrial DNA Copy Number : An Analysis of UK Biobank Data
AbstractHong, Y. S., Battle, S. L., Puiu, D., Shi, W., Pankratz, N., Zhao, D., Arking, D. E., & Guallar, E. (n.d.).Publication year
2023Journal title
Environmental health perspectivesVolume
131Issue
5Abstract~Medical Masks Versus N95 Respirators for Preventing COVID-19 Among Health Care Workers_04
AbstractLaine, C., Wee, C. C., Chang, S., Cotton, D., Chopra, V., Williams, S. V., Yu-Xiao, Y., Guallar, E., & Ross, E. A. (n.d.).Publication year
2023Journal title
Annals of internal medicineVolume
176Issue
7Abstract~Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization : A Cohort Study
AbstractKim, J., Kang, D., Park, H., Kang, M., Choi, K. H., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).Publication year
2023Journal title
Cardiovascular Drugs and TherapyVolume
37Issue
1Page(s)
141-150AbstractPurpose: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. Method: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10–20 mg or rosuvastatin 5–10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. Results: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86–1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74–1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. Conclusions: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults : insights from a comparative explainable study
AbstractNguyen, H. T., Vasconcellos, H. D., Keck, K., Reis, J. P., Lewis, C. E., Sidney, S., Lloyd-Jones, D. M., Schreiner, P. J., Guallar, E., Wu, C. O., Lima, J. A., & Ambale-Venkatesh, B. (n.d.).Publication year
2023Journal title
BMC Medical Research MethodologyVolume
23Issue
1AbstractBackground: Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. Methods: We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. Results: In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86–0.87 at 5 years, 0.79–0.81 at 10 years) than using baseline or last observed CS data (0.80–0.86 at 5 years, 0.73–0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. Conclusion: Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. Trial registration: ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome
AbstractSinn, D. H., Kang, D., Choi, S. C., Hong, Y. S., Zhao, D., Guallar, E., Park, Y., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2023Journal title
Clinical Gastroenterology and HepatologyVolume
21Issue
7Page(s)
1873-1880.e1AbstractBackground & Aims: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. Methods: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. Results: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42–1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). Conclusion: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.Obesity paradox in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy
AbstractLee, J. H., Kang, D., Ahn, J. S., Guallar, E., Cho, J., & Lee, H. Y. (n.d.).Publication year
2023Journal title
Journal of Cachexia, Sarcopenia and MuscleVolume
14Issue
6Page(s)
2898-2907AbstractBackground: The obesity paradox in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitor therapy has been observed, but its underlying mechanism is not fully understood. We aimed to investigate whether body composition affects the prognostic impact of obesity, as determined by body mass index (BMI), on survival. Methods: This retrospective study evaluated the data collected from Asian patients who were treated with immune checkpoint inhibitors for advanced non-small cell lung cancer between October 2015 and October 2021. We used abdominal cross-sectional imaging to calculate the skeletal muscle and visceral fat indices (cm2/m2) by dividing the cross-sectional areas of the skeletal muscle and visceral fat by the height squared. Cox proportional-hazards regression was performed to determine the correlation between BMI according to the Asia-Pacific classification, body composition metrics and overall survival. Results: We analysed the data of 820 patients (630 men and 190 women, with a mean age of 64.3 years [standard deviation: 10.4 years]) and observed 572 (69.8%) deaths with the 1-year mortality rate of 0.58 (95% confidence interval, 0.55–0.62). Obese BMI was associated with longer overall survival, independent of clinical covariates (hazard ratio, 0.64; 95% confidence interval: 0.52–0.80). The prognostic value of obese BMI remained after additional adjustments for skeletal muscle index (hazard ratio, 0.68; 95% confidence interval, 0.53–0.87) or visceral fat index (hazard ratio, 0.54; 95% confidence interval: 0.41–0.70). No association was observed between sex and the impact of BMI on overall survival (P-value for interaction >0.05). Conclusions: In Asian patients with advanced non-small cell lung cancer who received immune checkpoint inhibitors, obese BMI was associated with favourable overall survival independent of skeletal muscle or visceral fat mass.Oxidative Stress and Cardiovascular Risk Factors : The Coronary Artery Risk Development in Young Adults (CARDIA) Study
AbstractHeravi, A. S., Zhao, D., Michos, E. D., Doria De Vasconcellos, H., Ambale-Venkatesh, B., Lloyd-Jones, D., Schreiner, P. J., Reis, J. P., Shikany, J. M., Lewis, C. E., Ndumele, C. E., Guallar, E., Ouyang, P., Hoogeveen, R. C., Lima, J. A., Post, W. S., & Vaidya, D. (n.d.).Publication year
2023Journal title
AntioxidantsVolume
12Issue
3AbstractIntroduction—Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods—Oxidative stress was measured in 475 women and 266 men, aged 48–55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results—Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions—Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.Regression of nonalcoholic fatty liver disease is associated with reduced risk of incident diabetes : A longitudinal cohort study
AbstractSinn, D. H., Kang, D., Guallar, E., Choi, S. C., Hong, Y. S., Park, Y., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2023Journal title
PloS oneVolume
18Issue
7 JulyAbstractObjective Non-alcoholic fatty liver disease (NAFLD) is potentially reversible. However, whether improvement of NAFLD leads to clinical benefits remains uncertain. We investigated the association between regression of NAFLD and the risk of incident diabetes in a longitudinal way. Methods A cohort of 11,260 adults who had NAFLD at in an initial exam, had the second evaluation for NAFLD status at 1~2 years from an initial exam were followed up for incident diabetes from 2001 and 2016. NAFLD was diagnosed with abdominal ultrasound. Results At baseline, NAFLD was regressed in 2,559 participants (22.7%). During 51,388 person-years of follow-up (median 4 years), 1,768 participants developed diabetes. The fully adjusted hazard ratio (HR) for incident diabetes in participants with regressed NAFLD compared to those with persistent NAFLD was 0.81 [95% confidence interval (CI) 0.72–0.92]. When assessed by NAFLD severity, among participants with a low NAFLD fibrosis score (NFS) (< -1.455), participants with regressed NAFLD had a lower risk of incident diabetes than those with persistent NAFLD (HR 0.77, 95% CI 0.68–0.88). However, in participants with an intermediate to high NFS (≥ -1.455), the risk of incident diabetes was not different between NAFLD regression and persistence groups (HR 1.12, 95% CI 0.82–1.51). Conclusions Regression of NAFLD was associated with decreased risk of incident diabetes compared to persistent NAFLD. However, the benefit was evident only for NAFLD patients with low NFS. This suggests that early intervention for NAFLD, before advanced fibrosis is present, may maximize the metabolic benefit from NAFLD regression.